Hereditary Hemochromatosis and Its Elusive Natural History

From the Oak Ridge Associated Universities Inc, assigned to the Centers for Disease Control and Prevention, Epidemiology Program Office, Atlanta, Ga. The authors have no relevant financial interest in this article.

HEREDITARY hemochromatosis (HH) has long been described as a disorder of iron absorption that results in tissue iron deposition and cirrhosis of the liver.1 It has been assumed that HH results from a genetic trait that, given enough time, will inevitably express itself as increased absorption, transport, and storage of iron ultimately leading to organ damage. Based on this assumption, the approach to diagnosing HH has evolved away from analyzing liver biopsy specimens for signs of iron overload and liver damage to testing for specific genes or earlier phenotypic expression of traits that define increased risk for iron overload and disease. Thus, in the last 20 years, research has focused on determining the specific genetic loci and identifying the best laboratory test(s) to detect the disease early. Based on large studies of blood donors and outpatients, the prevalence of HH has been estimated at 3 to 5 per 1000 people.1 In 1996, 2 specific gene mutations (known as HFE) on chromosome 6 were identified and found to be associated with HH.2